Angelicin regulates LPS-induced inflammation via inhibiting MAPK/NF-κB pathways.

Angelicin is a furocoumarin found in Psoralea corylifolia L. fruit. The purpose of this study was to investigate the protective ability of angelicin against inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced in vivo acute lung injury model. The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 in the culture supernatants of RAW 264.7 cells were determined 24 h after LPS administration. ALI was induced by intratracheal instillation of LPS. Six hours after LPS inhalation, bronchoalveolar lavage fluid and lung tissue samples were obtained for enzyme-linked immunosorbent assay, histologic, and Western blotting analyses. The results showed that pretreatment with angelicin markedly downregulated TNF-α and IL-6 levels in vitro and in vivo, and significantly decreased the amount of inflammatory cells, lung wet-to-dry weight ratio, and myeloperoxidase activity in LPS-induced ALI mice. Furthermore, Western blotting analysis results demonstrated that angelicin blocked the phosphorylation of IκBα, NF-κBp65, p38 MAPK, and JNK in LPS-induced ALI. These results suggest that angelicin was potentially advantageous to prevent inflammatory diseases by inhibiting NF-κB and MAPK pathways. Our data indicated that angelicin might be a potential new agent for prevention of inflammatory reactions and diseases in the clinic.

Liu F ，Sun GQ ，Gao HY ，Li RS ，Soromou LW ，Chen N ，Deng YH ，Feng HH ... -  《-》

Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo.

Chu X ，Ci X ，Wei M ，Yang X ，Cao Q ，Guan M ，Li H ，Deng Y ，Feng H ，Deng X ... -  《-》

Protective effect of taraxasterol on acute lung injury induced by lipopolysaccharide in mice.

Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been reported to have potent anti-inflammatory properties. However, the effect of taraxasterol on lipopolysaccharide (LPS)-induced mice acute lung injury has not been investigated. The aims of this study were to investigate whether taraxasterol could ameliorate the inflammation response in LPS-induced acute lung injury and to clarify the possible mechanism. Male BALB/c mice were pretreated with taraxasterol 1h before intranasal instillation of LPS. 7h after LPS administration, the myeloperoxidase (MPO) in lung tissues, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were detected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46-p54 JNK, p42-p44 ERK, and p38 were determined by western blotting. The results showed that taraxasterol attenuated the infiltration of inflammatory cells, the activity of myeloperoxidase (MPO), lung wet/dry ratio, and the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in a dose-dependent manner. Additionally, western blotting results showed that taraxasterol inhibited the phosphorylation of IκB-α, p65 NF-κB, p46-p54 JNK, p42-p44 ERK, and p38 caused by LPS. Our data suggest that anti-inflammatory effects of taraxasterol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPK signaling pathways.

San Z ，Fu Y ，Li W ，Zhou E ，Li Y ，Song X ，Wang T ，Tian Y ，Wei Z ，Yao M ，Cao Y ，Zhang N ... -  《-》

Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice.

Phillyrin (Phil) is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. We tested the hypothesis that Phil modulates pulmonary inflammation in an ALI model induced by LPS. Male BALB/c mice were pretreated with or without Phil before respiratory administration with LPS, and pretreated with dexamethasone as a control. Cytokine release (TNF-α, IL-1β, and IL-6) and amounts of inflammatory cell in bronchoalveolar lavage fluid (BALF) were detected by ELISA and cell counting separately. Pathologic changes, including neutrophil infiltration, interstitial edema, hemorrhage, hyaline membrane formation, necrosis, and congestion during acute lung injury in mice were evaluated via pathological section with HE staining. To further investigate the mechanism of Phil anti-inflammatory effects, activation of MAPK and NF-κB pathways was tested by western blot assay. Phil pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by Phil pretreatment. In addition, Phil decreased the production of the proinflammatory cytokines including (TNF-α, IL-1β, and IL-6) and the concentration of myeloperoxidase (MPO) in lung tissues. Phil pretreatment also significantly suppressed LPS-induced activation of MAPK and NF-κB pathways in lung tissues. Taken together, the results suggest that Phil may have a protective effect on LPS-induced ALI, and it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways. Phil may be a new preventive agent of ALI in the clinical setting.

Zhong WT ，Wu YC ，Xie XX ，Zhou X ，Wei MM ，Soromou LW ，Ci XX ，Wang DC ... -  《-》

Isotetrandrine protects against lipopolysaccharide-induced acute lung injury by suppression of mitogen-activated protein kinase and nuclear factor-kappa B.

Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are pleiotropic regulator of many genes involved in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to reveal the protective effect of isotetrandrine (ITD), a small molecule inhibitor, on various aspects of LPS-induced inflammation in vitro and in vivo. In vitro, RAW 264.7 cells were pretreated with different dose of ITD 1 h before treatment with 1 mg/L of LPS. In vivo, to induce ALI, male BALB/c mice were injected intranasally with LPS and treated with ITD (20 and 40 mg/kg) 1 h before LPS. In vitro, the cytokine levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in supernatant were reduced by ITD. Meanwhile, in vivo, pulmonary inflammatory cell infiltration, myeloperoxidase activity, total cells, neutrophils, macrophages, along with the levels of tumor necrosis factor-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid were dose-dependently attenuated by ITD. Furthermore, our data showed that ITD significantly inhibited the activation of MAPK and NF-κB, which are induced by LPS in ALI model. These results suggested that ITD dose-dependently suppressed the severity of LPS-induced ALI by inactivation of MAPK and NF-κB, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process.

Liang XM ，Guo GF ，Huang XH ，Duan WL ，Zeng ZL ... -  《-》